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Background: In most low income countries there are twice as many cases of tuberculosis (TB) reported among men than among women, a difference commonly attributed to biological and epidemiological characteristics as well as socioeconomic and cultural barriers in access to health care. The World Health Organization has encouraged gender specific comparisons in TB rates to determine whether women with TB are less likely than men with TB to be diagnosed, reported, and treated. A study was undertaken to identify gender based differences in patients with pulmonary TB and to use this information to improve TB control efforts.Methods: Individuals with a cough for more than 2 weeks in southern Mexico were screened from March 1995 to April 2003. Clinical and mycobacteriological information (isolation, identification, drug susceptibility testing and IS6110 based genotyping, and spoligotyping) was collected from those with bacteriologically confirmed pulmonary TB. Patients were treated in accordance with official norms and followed to ascertain treatment outcome, retreatment, and vital status.Results: 623 patients with pulmonary TB were enrolled. The male:female incidence rate ratio for overall, reactivated, and recently transmitted disease was 1.58 (95% CI 1.34 to 1.86), 1.64 (95% CI 1.36 to 1.98), and 1.41 (95% CI 1.01 to 1.96), respectively. Men were more likely than women to default from treatment (adjusted OR 3.30, 95% CI 1.46 to 7.43), to be retreated (hazard ratio (HR) 3.15, 95% CI 1.38 to 7.22), and to die from TB (HR 2.23, 95% CI 1.25 to 3.99).Conclusions: Higher rates of transmitted and reactivated disease and poorer treatment outcomes among men are indicators of gender differentials in the diagnosis and treatment of pulmonary TB, and suggest specific strategies in endemic settings. [ABSTRACT FROM AUTHOR]

The utility of luciferase reporter mycobacteriophages (LRPs) for detection, identification, and antibiotic susceptibility testing of Mycobacterium tuberculosis was prospectively evaluated in a clinical microbiology laboratory in Mexico City, Mexico. Five hundred twenty-three consecutive sputum samples submitted to the laboratory during a 5-month period were included in this study. These specimens were cultivated in Middlebrook 7H9 (MADC), MGIT, and Löwenstein-Jensen (LJ) media. Of the 71 mycobacterial isolates recovered with any of the three media, 76% were detected with the LRPs, 97% were detected with the MGIT 960 method, and 90% were detected with LJ medium. When contaminated specimens were excluded from the analysis, the LRPs detected 92% (54 of 59) of the cultures. The median time to detection of bacteria was 7 days with both the LRPs and the MGIT 960 method. LRP detection of growth in the presence of p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) was used for selective identification of M. tuberculosis complex (MTC) and compared to identification with BACTEC 460. Using the LRP NAP test, 47 (94%) out of 50 isolates were correctly identified as tuberculosis complex. The accuracy and speed of LRP antibiotic susceptibility testing with rifampin, streptomycin, isoniazid, and ethambutol were compared to those of the BACTEC 460 method, and discrepant results were checked by the conventional proportion method. In total, 50 MTC isolates were tested. The overall agreement between the LRP and BACTEC 460 results was 98.5%. The median LRP-based susceptibility turnaround time was 2 days (range, 2 to 4 days) compared to 10.5 days (range, 7 to 16 days) by the BACTEC 460 method. Phage resistance was not detected in any of the 243 MTC isolates tested. Mycobacteriophage-based approaches to tuberculosis diagnostics can be implemented in clinical laboratories with sensitivity, specificity, and rapidity that compare favorably with those of the MGIT 960 and BACTEC 460 methods. The phages currently provide the fastest phenotypic assay for susceptibility testing.

Objective: To determine the impact of drug resistance (DR) on the clinical outcome and transmission of tuberculosis under programmatic conditions., Methods: Prospective cohort and molecular epidemiologic study in the Orizaba Health Jurisdiction of Mexico. Between March 1995 and July 1999, chronic coughers with positive acid-fast bacilli (AFB) detected in sputum smear underwent clinical and mycobacteriologic evaluation (species identification, drug susceptibility testing and IS6110-based genotyping). Treatment was provided in accordance with official norms., Results: Mycobacterium tuberculosis was isolated from 326/387 AFB-positive cases. The rate of DR was 24.2% and that of multidrug resistance (MDR, defined as resistance to both isoniazid and rifampin at least) was 7.7%; 78% were cured, 8% abandoned treatment, 6% failed treatment, and 5% died. An additional 13.5% received retreatment and 8.9% died during a median 28.6 months of follow up. Factors associated with DR by multivariate analysis were chronicity of tuberculosis (OR 4.8, 95%CI 2.7-8.4, P < 0.001), age >40 years (OR 1.9, 95%CI 1.1-3.2, P = 0.02) and indigenous origin (OR 0.3, 95%CI 0.13-0.75, P = 0.01). Cox-adjusted relative risks showed that MDR (RR 2.5, 95%CI 1.02-6.16, P = 0.04), HIV infection (RR 31.3, 95%CI 11.6-84.8, P < 0.001), and chronicity of tuberculosis (RR 2.1, 95%CI 1.0-4.4, P = 0.06) were associated with mortality, controlling for age. Predictors of retreatment were DR (not including MDR) (RR 2.2 95%CI 0.89-5.31, P < 0.087), MDR (RR 12.6, 95%CI 5.46-28.88, P < 0.001), and living in a household with an earthen floor (RR 2.8, 95%CI 1.27-6.13, P = 0.011). Being infected with MDR-TB was the only factor associated with a decreased likelihood of being in an RFLP cluster (OR 0.31, 95%CI 0.12-0.81, P = 0.02)., Conclusions: Although MDR-TB may have a decreased propensity to spread and cause disease, it has a profoundly negative impact on tuberculosis control.

Background: Consequences of drug-resistant tuberculosis (TB) in developing countries using directly observed treatment, short-course (DOTS), are not well defined., Objective: To determine the impact of drug resistance on clinical outcome and transmission of TB under programmatic conditions., Patients and Methods: A prospective cohort and molecular epidemiologic study was conducted in southern Mexico. Between March 1995 and February 1998 all patients with persistent cough whose sputa had acid-fast bacilli (AFB) underwent clinical and mycobacteriologic evaluation (species identification, drug susceptibility testing, and IS6110-based genotyping). Treatment was provided in accordance with Mexico's National Tuberculosis Program. Clinical and microbiologic outcomes and molecular epidemiologically defined transmission were measured., Results: Mycobacterium tuberculosis was isolated from 238 of the 284 AFB smear-positive persons. The overall rate of resistance was 28.4% (new, 20.7%; retreated, 54.7%), and 10.8% (new, 3.3%; retreated, 35.8%) had multi-drug-resistant TB (ie, resistance to isoniazid and rifampin). After treatment, 75% (new, 81.0%; retreated, 52.8%) were cured, 8% (new, 7.8%; retreated, 7.5%) abandoned therapy, 9% (new, 3.9%; retreated, 28.3%) had treatment failure, and 4% (new, 3.3%; retreated, 7.5%) died. Another 2% of patients relapsed, and 9% died during a median of 24.4 months of follow-up. Drug-resistance was a strong independent risk factor for treatment failure. Being infected with multi-drug-resistant TB was the only factor associated with a decreased likelihood of being in a restriction fragment length polymorphism cluster., Conclusions: Despite the use of DOTS, patients with drug-resistant TB had a dramatically increased probability of treatment failure and death. Although multi-drug-resistant TB may have a decreased propensity to spread and cause disease, it has a profoundly negative impact on TB control.

Setting: A community in Southern Mexico with a high prevalence of tuberculosis., Objective: To characterize the transmission dynamics in a region with a DOTS-based tuberculosis control program., Design: Community-based screening of chronic coughers between 1 March 1995 and 31 August 1996. Individuals with acid-fast bacilli (AFB) in their sputum were enrolled, interviewed, and had mycobacterial cultures and fingerprinting performed. In-depth interviews were conducted on all persons with DNA fingerprinting., Results: AFB smears were performed on 1424 individuals, 124 of whom were microbiologically confirmed. Of the 95 cases for whom bacterial DNA fingerprints were available, 38 were in clusters. The largest cluster involved seven individuals who were members of a social network centered on a series of unlicensed bars., Conclusion: This population-based molecular epidemiologic study showed that a focus of transmission within a social network accounted for one fourth of transmission which rapidly progressed to disease. These observations raise questions about the potential benefit of targeted tuberculosis control interventions in health jurisdictions approaching WHO-defined DOTS benchmarks.

Background: Tuberculosis (TB) rates remain high in regions of Southern Mexico despite the existence of a National Tuberculosis Program. Understanding TB epidemiology in such settings would assist in the design of improved TB control and highlight the challenges confronting TB control in developing countries., Methods: We conducted a retrospective review of treatment control cards from 1991 to 1994 in five municipalities in a semiurban region of Southern Mexico., Results: The relatively high rate of TB observed, 42.6 per 100,000 inhabitants, did not change significantly during the study period. Cure rates among new cases were 79% and significantly lower among retreatment cases (62%). Directly observed therapy (DOT) was administered to 84% of patients. Approximately one-half of the retreatment cases who were not cured were compliant with therapy, suggesting that drug resistance contributed to these poor results. Of particular concern was a core group of 16 patients who had received at least three treatments., Conclusions: This region of Mexico has persistently high TB rates despite a DOT-based TB control programme which achieves an overall cure rate of 77%. There exist many retreatment cases for whom cure rates are significantly lower. These cases may serve as a core group for the dissemination of drug resistant TB. The control programme is being reinforced by a nominal register of patients, decreasing administrative barriers for drug supply to individual patients and the availability of mycobacteria cultures. In addition to these measures, in regions which are approaching the levels of efficacy recommended by the WHO it may be appropriate to consider focusing efforts on the identification and treatment of chronic cases.

Setting: San Francisco, California., Objective: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons., Design: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews., Results: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons., Conclusion: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.